DOI: 10.1128/jvi.74.4.1961-1972.2000. Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus

Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus

10.1128/jvi.74.4.1961-1972.2000

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The human immunodeficiency virus envelope glycoproteins, gp120 and gp41, function in cell entry by binding to CD4 and a chemokine receptor on the cell surface and orchestrating the direct fusion of the viral and target cell membranes. On the virion surface, three gp120 molecules associate noncovalently with the ectodomain of the gp41 trimer to form the envelope oligomer. Although an atomic-level structure of a monomeric gp120 core has been determined, the structure of the oligomer is unknown. Here, the orientation of gp120 in the oligomer is modeled by using quantifiable criteria of carbohydrate exposure, occlusion of conserved residues, and steric considerations with regard to the binding of the neutralizing antibody 17b. Applying similar modeling techniques to influenza virus hemagglutinin suggests a rotational accuracy for the oriented gp120 of better than 10°. The model shows that CD4 binds obliquely, such that multiple CD4 molecules bound to the same oligomer have their membrane-spanning portions separated by at least 190 Å. The chemokine receptor, in contrast, binds to a sterically restricted surface close to the trimer axis. Electrostatic analyses reveal a basic region which faces away from the virus, toward the target cell membrane, and is conserved on core gp120. The electrostatic potentials of this region are strongly influenced by the overall charge, but not the precise structure, of the third variable (V3) loop. This dependence on charge and not structure may make electrostatic interactions between this basic region and the cell difficult to target therapeutically and may also provide a means of viral escape from immune system surveillance.

Bibliography

Kwong, P. D., Wyatt, R., Sattentau, Q. J., Sodroski, J., & Hendrickson, W. A. (2000). Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus. Journal of Virology, 74(4), 1961â1972.

Authors 5

Peter D. Kwong (first)
Richard Wyatt (additional)
Quentin J. Sattentau (additional)
Joseph Sodroski (additional)
Wayne A. Hendrickson (additional)

References 64 Referenced 225

10.1016/S0022-2836(05)80360-2
10.1016/0166-3542(88)90035-6
10.1016/S0006-3495(96)79280-9
10.1038/376092a0
Brunger A. T. X-PLOR version 3.1 manual. 1993 Yale University New Haven Conn
10.1038/371037a0
10.1074/jbc.271.14.8236
10.1074/jbc.270.5.2224
Chamow S. Duliege A. Ammann A. Kahn J. Allen J. Eichberg J. Byrn R. Capon D. Ward R. Ashenazi A. CD4 immunoadhesins in anti-HIV therapy: new developments.Int. J. Cancer Suppl. 7 1992 69 72 / Int. J. Cancer Suppl. / CD4 immunoadhesins in anti-HIV therapy: new developments by Chamow S. (1992)
10.1016/S0092-8674(00)80205-6
Chan D. C. Kim P. S. HIV entry and its inhibition.Nat. Struct. Biol. 5 1998 276 279 / Nat. Struct. Biol. / HIV entry and its inhibition by Chan D. C. (1998)
10.1038/312763a0
10.1021/jm00034a007
10.1128/JVI.72.1.279-285.1998
10.1128/JVI.72.10.8437-8445.1998
10.1128/JVI.72.9.7620-7625.1998
10.1128/JVI.72.2.1160-1164.1998
10.1016/S0092-8674(00)80577-2
10.1126/science.277.5332.1662
10.1126/science.272.5263.872
10.1016/0042-6822(87)90449-1
10.1099/0022-1317-70-8-2215
10.1097/00002030-199402000-00005
10.1089/aid.1996.12.1463
10.1073/pnas.93.7.3099
Jansen R. W. Schols D. Pauwels R. De Clercq E. Meijer D. K. Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity.Mol. Pharmacol. 44 1993 1003 1007 / Mol. Pharmacol. / Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity by Jansen R. W. (1993)
10.1107/S0108767390010224
10.1038/3293
10.1038/312767a0
10.1128/JVI.73.10.8120-8126.1999
10.1089/aid.1993.9.1087
10.1038/31405
10.1038/346277a0
10.1016/S0968-0004(00)89042-8
10.1126/science.2452480
10.1128/JVI.72.5.3623-3634.1998
10.1128/jvi.65.3.1133-1140.1991
10.1126/science.276.5309.51
10.1128/JVI.74.4.1948-1960.2000
10.1021/bi972012b
10.1002/jcc.540120405
10.1002/prot.340110407
10.1089/aid.1993.9.167
10.1084/jem.183.2.473
10.1126/science.280.5371.1949
10.1073/pnas.95.13.7682
10.1073/pnas.82.4.1104
10.1016/S0969-2126(99)80020-3
Staudinger R. Abraham N. G. Levere R. D. Kappas A. Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs.Proc. Assoc. Am. Physicians 108 1996 47 54 / Proc. Assoc. Am. Physicians / Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs by Staudinger R. (1996)
10.1128/JVI.72.8.6332-6338.1998
10.3109/10611869609046269
10.1073/pnas.94.23.12303
10.1128/jvi.67.7.3978-3988.1993
10.1016/0022-2836(90)90234-D
10.1016/S1097-2765(00)80159-8
10.1038/387426a0
10.1016/S0006-2952(97)00157-3
10.1073/pnas.91.21.9770
10.1038/289366a0
10.1038/387527a0
10.1038/384179a0
10.1038/31514
10.1128/jvi.67.8.4557-4565.1993
10.1002/(SICI)1097-0134(1999)37:3 <66::AID-PROT10>3.0.CO;2-K

Dates

Type	When
Created	23 years ago (July 27, 2002, 6:06 a.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 12:30 a.m.)
Indexed	2 months, 1 week ago (June 10, 2025, 1:27 p.m.)
Issued	25 years, 6 months ago (Feb. 15, 2000)
Published	25 years, 6 months ago (Feb. 15, 2000)
Published Print	25 years, 6 months ago (Feb. 15, 2000)

Funders 0

None

BibTeX

@article{Kwong_2000, title={Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus}, volume={74}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.74.4.1961-1972.2000}, DOI={10.1128/jvi.74.4.1961-1972.2000}, number={4}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Kwong, Peter D. and Wyatt, Richard and Sattentau, Quentin J. and Sodroski, Joseph and Hendrickson, Wayne A.}, year={2000}, month=feb, pages={1961–1972} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        6,
        10
      ]
    ],
    "date-time": "2025-06-10T17:27:03Z",
    "timestamp": 1749576423641
  },
  "reference-count": 64,
  "publisher": "American Society for Microbiology",
  "issue": "4",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2000,
            2,
            15
          ]
        ],
        "date-time": "2000-02-15T00:00:00Z",
        "timestamp": 950572800000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        2,
        15
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>The human immunodeficiency virus envelope glycoproteins, gp120 and gp41, function in cell entry by binding to CD4 and a chemokine receptor on the cell surface and orchestrating the direct fusion of the viral and target cell membranes. On the virion surface, three gp120 molecules associate noncovalently with the ectodomain of the gp41 trimer to form the envelope oligomer. Although an atomic-level structure of a monomeric gp120 core has been determined, the structure of the oligomer is unknown. Here, the orientation of gp120 in the oligomer is modeled by using quantifiable criteria of carbohydrate exposure, occlusion of conserved residues, and steric considerations with regard to the binding of the neutralizing antibody 17b. Applying similar modeling techniques to influenza virus hemagglutinin suggests a rotational accuracy for the oriented gp120 of better than 10\u00b0. The model shows that CD4 binds obliquely, such that multiple CD4 molecules bound to the same oligomer have their membrane-spanning portions separated by at least 190 \u212b. The chemokine receptor, in contrast, binds to a sterically restricted surface close to the trimer axis. Electrostatic analyses reveal a basic region which faces away from the virus, toward the target cell membrane, and is conserved on core gp120. The electrostatic potentials of this region are strongly influenced by the overall charge, but not the precise structure, of the third variable (V3) loop. This dependence on charge and not structure may make electrostatic interactions between this basic region and the cell difficult to target therapeutically and may also provide a means of viral escape from immune system surveillance.</jats:p>",
  "DOI": "10.1128/jvi.74.4.1961-1972.2000",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        27
      ]
    ],
    "date-time": "2002-07-27T10:06:37Z",
    "timestamp": 1027764397000
  },
  "page": "1961-1972",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 225,
  "title": "Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus",
  "prefix": "10.1128",
  "volume": "74",
  "author": [
    {
      "given": "Peter D.",
      "family": "Kwong",
      "sequence": "first",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Department of Biochemistry and Molecular Biophysics1 and"
        }
      ]
    },
    {
      "given": "Richard",
      "family": "Wyatt",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School,2 and"
        }
      ]
    },
    {
      "given": "Quentin J.",
      "family": "Sattentau",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 3-->Centre d'Immunologie de Marseille-Luminy, 13288 Marseille Cedex 9, France3"
        }
      ]
    },
    {
      "given": "Joseph",
      "family": "Sodroski",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School,2 and"
        },
        {
          "name": "<!--label omitted: 4-->Department of Immunology and Infectious Diseases, Harvard School of Public Health,4 Boston, Massachusetts 02115; and"
        }
      ]
    },
    {
      "given": "Wayne A.",
      "family": "Hendrickson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Department of Biochemistry and Molecular Biophysics1 and"
        },
        {
          "name": "<!--label omitted: 5-->Howard Hughes Medical Institute,5 Columbia University, New York, New York 10032;"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(05)80360-2"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-3542(88)90035-6"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(96)79280-9"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/376092a0"
    },
    {
      "key": "e_1_3_2_6_2",
      "unstructured": "Brunger\nA. T.\nX-PLOR version 3.1 manual.\n1993\nYale University\nNew Haven Conn"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/371037a0"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.14.8236"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.5.2224"
    },
    {
      "key": "e_1_3_2_10_2",
      "first-page": "69",
      "article-title": "CD4 immunoadhesins in anti-HIV therapy: new developments",
      "volume": "7",
      "author": "Chamow S.",
      "year": "1992",
      "unstructured": "Chamow S. Duliege A. Ammann A. Kahn J. Allen J. Eichberg J. Byrn R. Capon D. Ward R. Ashenazi A. CD4 immunoadhesins in anti-HIV therapy: new developments.Int. J. Cancer Suppl. 7 1992 69 72",
      "journal-title": "Int. J. Cancer Suppl."
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80205-6"
    },
    {
      "key": "e_1_3_2_12_2",
      "first-page": "276",
      "article-title": "HIV entry and its inhibition",
      "volume": "5",
      "author": "Chan D. C.",
      "year": "1998",
      "unstructured": "Chan D. C. Kim P. S. HIV entry and its inhibition.Nat. Struct. Biol. 5 1998 276 279",
      "journal-title": "Nat. Struct. Biol."
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/312763a0"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jm00034a007"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.1.279-285.1998"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.10.8437-8445.1998"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.9.7620-7625.1998"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.2.1160-1164.1998"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80577-2"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.277.5332.1662"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.272.5263.872"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(87)90449-1"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/0022-1317-70-8-2215"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1097/00002030-199402000-00005"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/aid.1996.12.1463"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.7.3099"
    },
    {
      "key": "e_1_3_2_27_2",
      "first-page": "1003",
      "article-title": "Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity",
      "volume": "44",
      "author": "Jansen R. W.",
      "year": "1993",
      "unstructured": "Jansen R. W. Schols D. Pauwels R. De Clercq E. Meijer D. K. Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity.Mol. Pharmacol. 44 1993 1003 1007",
      "journal-title": "Mol. Pharmacol."
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0108767390010224"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/3293"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/312767a0"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.73.10.8120-8126.1999"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/aid.1993.9.1087"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/31405"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/346277a0"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0968-0004(00)89042-8"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2452480"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.5.3623-3634.1998"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.65.3.1133-1140.1991"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.276.5309.51"
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.74.4.1948-1960.2000"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi972012b"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540120405"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/prot.340110407"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/aid.1993.9.167"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.183.2.473"
    },
    {
      "key": "e_1_3_2_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.280.5371.1949"
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.13.7682"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.82.4.1104"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0969-2126(99)80020-3"
    },
    {
      "key": "e_1_3_2_50_2",
      "first-page": "47",
      "article-title": "Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs",
      "volume": "108",
      "author": "Staudinger R.",
      "year": "1996",
      "unstructured": "Staudinger R. Abraham N. G. Levere R. D. Kappas A. Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs.Proc. Assoc. Am. Physicians 108 1996 47 54",
      "journal-title": "Proc. Assoc. Am. Physicians"
    },
    {
      "key": "e_1_3_2_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.8.6332-6338.1998"
    },
    {
      "key": "e_1_3_2_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.3109/10611869609046269"
    },
    {
      "key": "e_1_3_2_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.23.12303"
    },
    {
      "key": "e_1_3_2_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.67.7.3978-3988.1993"
    },
    {
      "key": "e_1_3_2_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(90)90234-D"
    },
    {
      "key": "e_1_3_2_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(00)80159-8"
    },
    {
      "key": "e_1_3_2_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/387426a0"
    },
    {
      "key": "e_1_3_2_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-2952(97)00157-3"
    },
    {
      "key": "e_1_3_2_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.21.9770"
    },
    {
      "key": "e_1_3_2_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/289366a0"
    },
    {
      "key": "e_1_3_2_61_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/387527a0"
    },
    {
      "key": "e_1_3_2_62_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/384179a0"
    },
    {
      "key": "e_1_3_2_63_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/31514"
    },
    {
      "key": "e_1_3_2_64_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.67.8.4557-4565.1993"
    },
    {
      "key": "e_1_3_2_65_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0134(1999)37:3 <66::AID-PROT10>3.0.CO;2-K"
    }
  ],
  "container-title": "Journal of Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.74.4.1961-1972.2000",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.74.4.1961-1972.2000",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        3,
        5
      ]
    ],
    "date-time": "2022-03-05T05:30:36Z",
    "timestamp": 1646458236000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/JVI.74.4.1961-1972.2000"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        2,
        15
      ]
    ]
  },
  "references-count": 64,
  "journal-issue": {
    "issue": "4",
    "published-print": {
      "date-parts": [
        [
          2000,
          2,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/JVI.74.4.1961-1972.2000"
  ],
  "URL": "http://dx.doi.org/10.1128/JVI.74.4.1961-1972.2000",
  "relation": {},
  "ISSN": [
    "0022-538X",
    "1098-5514"
  ],
  "subject": [],
  "container-title-short": "J Virol",
  "published": {
    "date-parts": [
      [
        2000,
        2,
        15
      ]
    ]
  },
  "assertion": [
    {
      "value": "1999-06-25",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1999-11-17",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2000-02-15",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}